Preliminary work in this laboratory has demonstrated a clear relationship between the calcium contents of various pools of cellular calcium and contractile behavior of rat left ventricular muscle. We have studied these characteristics using a radioisotope (45 Ca ions method to delineate calcium content and exchange in the small strips of ventricular tissue. I propose to continue studies which would be further tests of the simple model: a) Acute studies will involve immediate alteration of contractile response using appropriate pharmacological agents, altered pH, O2 tension and temperature. b) Chronic studies involving induction of cardiac hypertrophy and failure by means of aortic constriction or injection of chemical agents (phenylhydrazine, isoproterenol). In all experiments, contractile response and calcium content and exchange are determined in the very same strip of ventricular muscle. The studies proposed will result in development of a new understanding of the relative relationships between compartments of cellular calcium and contractility. If the model developed in normal tissue can be adequately applied to hypertrophied and failing myocardium, tests of therapeutic agents and procedures are then possible.